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Post-Transplant Cyclophosphamide in Patients Aged >/= 65 Years Undergoing Haploidentical Transplant

Phase 1
Recruiting
Conditions
Hematologic Malignancies
Interventions
Registration Number
NCT05849207
Lead Sponsor
Ronald Paquette
Brief Summary

The purpose of this phase 1 study is to determine the optimal dose of the immune suppressive drug, cyclophosphamide, following standard allogeneic stem cell transplant in patients aged \>/= 65 years with hematologic malignancies.

Detailed Description

The patients will receive a standard dose, or a reduced amount of the immune suppressive drug, cyclophosphamide, that is routinely administered after the transplant procedure. The following procedures will be performed: cardiac MRI scans and/or transthoracic echocardiogram (TTE); laboratory tests, geriatric assessments and tests to measure strength and stability.

Participation in the study is expected to last up to one year with follow-up visits occurring on Day +30, Day +100, Day +180 and Day +365 following allogenic stem cell transplant.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
26
Inclusion Criteria
  • Patient age >/= 65 years
  • Patient and related Donor (if applicable) sign the Informed Consent Form for the study. If donor is unrelated, donor does not sign Informed Consent Form and this will not affect recipient study eligibility.
  • Patient meets standard criteria for allogeneic stem cell transplant
  • Patient is deemed suitable to receive Flu/TBI 800 conditioning regimen as standard of care transplant
  • Donor is willing to donate peripheral blood stem cells
Exclusion Criteria
  • Patient has a diagnosis of myelofibrosis

  • Patient has high titer antibodies (>10,000 mean fluorescent intensity) against one or more donor HLA antigens

  • Patient has undergone prior autologous or allogeneic stem cell transplant

  • Inability to collect at least 3 x 10^6 CD34+ PBSCs/kg recipient weight from the donor

  • Requiring sedation for cardiac MRIs.

  • Prohibited Implants and/or Devices:

    • Mechanical, magnetic or electrical activated implants (i.e. cardiac pacemakers, neurostimulators and infusion pumps)
    • Ferromagnetic implants and ferromagnetic foreign bodies, such as intracranial, aneurysm clips, shrapnel and intraocular metal chips as these could become dislodged.
  • Subjects with claustrophobia, problems being in enclosed spaces, or inability to lie supine.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Open ArmCyclophosphamideAll patients will receive cyclophosphamide on Day +3 and Day +4 following transplant.
Primary Outcome Measures
NameTimeMethod
Maximum grade acute GVHD by day +100 by Modified Keystone Criteria100 days post-transplant

Evaluate the frequency of grade III/IV acute GVHD using Modified Keystone Criteria

Secondary Outcome Measures
NameTimeMethod
Relapse1-year post-transplant

Percentage of patients who relapse by year 1

Change in cardiac functionFrom 60 days prior to transplant to 365 days post-transplant

Change in cardiac (heart) injury defined by any of an increase in T1 time \> 500 ms from pre-transplant imaging, T2 time \> 5 ms from pre-transplant imaging, or a decrease in left ventricular ejection fraction \> 10% of the original measurement to below 53% from post-transplant imaging.

Change in active daily livingFrom 60 days prior to transplant to 365 days post-transplant

Change in function over time as determined by Lawton Activities of Daily Living questionnaire.

- Patients will choose either 0 or 1 to rate their level of function with 1 being the highest level of function.

Change in painFrom 60 days prior to transplant to 365 days post-transplant

Change in pain over time as determined by the Patient-Reported Outcomes Measurement Information System (PROMIS) Cancer Function Brief 3-Dimensional Profile.

- Patients will rate their level of pain using a scale from 0 to 10 with 10 being the highest level of pain.

Change in cognitive functionFrom 60 days prior to transplant to 365 days post-transplant

Change in cognitive function over time using the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognition questionnaire.

-Patients will rate their cognitive ability on a scale of 1 to 5 with 5 representing the least amount of difficulty.

Non-Relapse mortality100 days post-transplant

Rate of treatment-related mortality

Change in grip strengthFrom 60 days prior to transplant to 365 days post-transplant

Change in grip strength as measured using the Jamar dynamometer (device used to measure grip)

Overall Survival (OS)1-year post-transplant

Overall survival at 1 year

Graft Versus Host Disease (GVHD)-free and Relapse Free Survival1-year post- transplant

Percentage of patients without relapse or GVHD at 1 year

Change in mental healthFrom 60 days prior to transplant to 365 days post-transplant

Change in mental health over time using the Patient-Reported Outcomes Measurement Information System (PROMIS) 29 Depression Questionnaire.

- Patients will rate their level of depression on a scale of 1 to 5 with 5 representing the greatest level of depression.

Time to neutrophil and platelet engraftment60 days post-transplant

Days to neutrophil and platelet engraftment since transplant

Chronic Graft Versus Host Disease (GVHD) at 1 year1-year post-transplant

* Rate and severity of patients with chronic GVHD at day 365 post-transplantation.

* Chronic GVHD is when the donated stem cells attack the body after 100 days post-transplant. Chronic GVHD is defined by NIH Consensus Criteria for chronic GVHD.

Change in functionFrom 60 days prior to transplant to 365 days post-transplant

Change in function over time as determined by the Patient-Reported Outcomes Measurement Information System (PROMIS) Cancer Function Brief 3-Dimensional Profile.

- Patients will rate their physical condition and fatigue using an inverse 5-item likert scale where 5 represents the highest level of function or the greatest amount of impact on function.

Change in physical functionFrom 60 days prior to transplant to 365 days post-transplant

Change in lower limb functioning over time as evaluated by the Short Physical performance Battery. (SPPB).

- Patients will complete a series of tests evaluating balance, speed and standing capabilities. Patients will be rated using a scale of 0 to 12 where a score of less than 10 indicates mobility limitations.

Trial Locations

Locations (1)

Cedars-Sinai Medical Center

🇺🇸

Los Angeles, California, United States

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